MDR1 in taste buds of rat vallate papilla: functional, immunohistochemical, and biochemical evidence.
Multidrug resistance P-glycoprotein (MDR1) is a membrane protein of 150-170 kDa that catalyzes the ATP-driven efflux of hydrophobic xenobiotics, including fluorescent dyes, from cells. Expressed in many epithelial tissues and in the endothelia of the blood-brain barrier, the MDR1 protein provides major routes of detoxification. We found that taste cells of the rat vallate papilla (VP; posterior tongue) had only a slow increase in fluorescence due to uptake of the hydrophobic dye calcein acetoxymethyl ester. However, the development of fluorescence was accelerated two- to threefold by substrates and/or inhibitors of MDR1, such as verapamil, tamoxifen, and cyclosporin A, and by addition of the transport-blocking antibody to MDR1, UIC2. Western blots of vallate tissue rich in taste buds with the MDR1-specific monoclonal antibodies C219 and C494 revealed an immunoreactive protein at approximately 170 kDa. In contrast, the lingual epithelium surrounding the VP showed a much weaker band with these antibodies. Furthermore, using the antibodies C494 and UIC2 with tissue sections, MDR1-like immunoreactivity was found in taste cells. These results show that MDR1 is present and functional in vallate taste cells of the rat. MDR1-related transport may achieve active elimination of xenobiotics from the sensory cells and thereby protect the peripheral taste organs from potentially harmful molecules contained in an animal's food.
Jakob
I
I
Department of Physiology, Saar University, Homburg, Germany.
Hauser
I A
IA
Thévenod
F
F
Lindemann
B
B
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D003239:Connective Tissue Cells / Q000166:cytology / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005452:Fluoresceins / Q000493:pharmacokinetics; D005456:Fluorescent Dyes; D007074:Immunoglobulin G / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008856:Microscopy, Fluorescence; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology; D013650:Taste Buds / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014059:Tongue / Q000166:cytology / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007074:Immunoglobulin G; D013629:Tamoxifen; D016572:Cyclosporine; D014700:Verapamil; C007740:fluorexon